Spa-1和Ki-67在乳房外Paget病肿瘤组织中的表达

目的 探讨Spa-1在乳房外Paget病发生和转移中可能的作用.方法 取17例原位乳房外Paget病和12例侵袭性乳房外Paget病患者皮损及9例正常人皮肤组织,用免疫组化分别检测Spa-1和Ki-67的表达.结果 Spa-1在胞质中显色,Ki-67在胞核中显色.Spa-1和Ki-67仅少量表达于正常人皮肤基底层,在乳房外Paget病肿瘤组织中的表达明显高于正常人皮肤(P<0.01).Spa-1在侵袭性乳房外Paget病肿瘤组织中表达明显高于原位乳房外Paget病(P<0.01).乳房外Paget病肿瘤组织中Spa-1的表达与Ki-67的表达呈正相关.结论 Spa-1在乳房外Paget病的发生发展中可能起作用.

Abstract：

Objective To investigate the potential role of Spa-1 in the development and metastasis of EMPD.Methods Tissue specimens were resected from 17 patients with primary EMPD,12 patients with invasive EMPD and 9 normal human controls.Immunohistochemistry was performed to measure the expression of spa-1 and Ki-67.Results Positive staining was observed for Spa-1 in cytoplasm,and for Ki-67 in cell nuclei.Spa-1 and Ki-67 were weakly expressed in the basal layer of normal skin.The expression of Spa-1 and Ki-67 in EMPD tissue were statistically higher than those in the normal control tissue (both P<0.01).Increased expression of Spa-1 was noted in invasive EMPD tissue compared with in situ EMPD tissue.The expression of Spa-1 was positively correlated with that of Ki-67 in the tissue of EMPD.Conclusion Spa-1 may play a certain role in the initiation and progression of EMPD.     

非肿瘤期和肿瘤期蕈样肉芽肿皮损中CXCR3和CD1a的表达

目的 探讨不同分期蕈样肉芽肿皮损中表皮内CXC趋化因子受体3(CXCR3)和CD1a的表达情况.方法 免疫组化法分别检测16例正常人对照、16例非肿瘤期和8例肿瘤期蕈样肉芽肿患者皮损表皮内CXCR3和CD1a的表达情况.结果 当蕈样肉芽肿由斑片/斑块期进展至肿瘤期,表皮内淋巴细胞的CXCR3阳性率由38.9%降至17.5%,两者差异有统计学意义.CD1a在正常对照、非肿瘤期蕈样肉芽肿、肿瘤期蕈样肉芽肿表皮内每高倍视野分别含朗格汉斯细胞7.3、10.6、6.7个.非肿瘤期蕈样肉芽肿表皮内朗格汉斯细胞数量明显多于肿瘤期与正常人对照,肿瘤期与正常人对照差异无统计学意义.结论 蕈样肉芽肿中亲表皮现象与Th1相关趋化因子受体CXCR3及表皮内朗格汉斯细胞数量有关.

Abstract：

Objective To investigate the expressions of CXC chemokine receptor 3 (CXCR3) and CD1a in skin lesions of different stages of mycosis fungoides (MF). Methods The expression and distribution profiles of CD1a and CXCR3 were detected by immunohistochemistry in the epidermis of skin samples from 16 normal human controls, 16 patients with non-tumor (patch/plaque) stage MF and 8 patients with tumor stage MF. Results With the progression of MF from patch/plaque stage to tumor stage, the positivity rate of CXCR3 in intraepithelial neoplastic cells in lesions dropped from 38.9% to 17.5% (P ＜ 0.05). The average number of intraepithelial Langerhans cells (LCs) per high power field (HPF) in skin samples was 10.6 in patch/plaque stage MF, significantly higher than that in normal control (7.3) and tumor stage MF (6.7), while no significant difference was found between normal control and tumor stage MF specimens. Conclusion The epidermotropism in MF may be associated with the expression of T-helper (Th) 1-associated chemokine receptor (CXCR3) and quantity of intraepithelial LCs.     

乳房外Paget病并发尖锐湿疣

报告1例乳房外Paget病(EMPD)并发尖锐湿疣(CA)。患者男,72岁。阴茎、阴囊浸润性红斑伴瘙痒4年,1个月前阴茎、阴囊、龟头及包皮出现多个疣状赘生物。皮损组织病理检查:(阴茎根部皮损)表皮棘层肥厚,表皮突延长,表皮内有不等量的Paget细胞,呈圆形或卵圆形,无细胞间桥,胞质丰富,淡染,细胞核较大,伴慢性炎症;(阴茎赘生物)鳞状上皮呈乳头样增生伴挖空样细胞。免疫组化示:CK7(+)、CerbB2(+)、CK5/6(+)、P53(+)、Ki-67约20%(+)、CK20(-)、s-100蛋白(-)及HMB45(-)。诊断:EMPD并发CA。     

准分子激光治疗白癜风的临床疗效与安全性研究

Objective To assess the efficacy and safety of 308 nm excimer laser in the treatment of different types of vitiligo at different stages. Methods A total of 128 patients with vitiligo, who had 317 depigmented patches, were recruited in this study and treated with 308 nm excimer laser once a week for at least 8 weeks. The degree of repigmentation was evaluated and adverse effects were recorded at the end of every treatment and last treatment. Results All patients received efficacy and safety evaluation. Of the 317 patches, 97.5% achieved repigmentation at different degrees, 71.8% got more than 25% repigmentation, and 50.8% got more than 75% repigmentation. The degree of repigmentation increased with the number of treatments. A better response was observed in the lesions on the face and neck than those on the mink and limbs, and in short-duration (<1 year) lesions than in long-duration (≥1 year) lesions. And the lesions on extremities and mueosa showed a poorer response compared with those at other sites. There was no statistical difference in clinical efficacy between active vitiligo and stable vitiligo, or between adults and children. Moreover, the treatment was well tolerated. Conclusion 308 nm excimer laser is effective in the treatment of vitiligo with rapid onset, favorable tolerability and few adverse effects.     

准分子激光治疗白癜风的临床疗效与安全性研究

Objective To assess the efficacy and safety of 308 nm excimer laser in the treatment of different types of vitiligo at different stages. Methods A total of 128 patients with vitiligo, who had 317 depigmented patches, were recruited in this study and treated with 308 nm excimer laser once a week for at least 8 weeks. The degree of repigmentation was evaluated and adverse effects were recorded at the end of every treatment and last treatment. Results All patients received efficacy and safety evaluation. Of the 317 patches, 97.5% achieved repigmentation at different degrees, 71.8% got more than 25% repigmentation, and 50.8% got more than 75% repigmentation. The degree of repigmentation increased with the number of treatments. A better response was observed in the lesions on the face and neck than those on the mink and limbs, and in short-duration (<1 year) lesions than in long-duration (≥1 year) lesions. And the lesions on extremities and mueosa showed a poorer response compared with those at other sites. There was no statistical difference in clinical efficacy between active vitiligo and stable vitiligo, or between adults and children. Moreover, the treatment was well tolerated. Conclusion 308 nm excimer laser is effective in the treatment of vitiligo with rapid onset, favorable tolerability and few adverse effects.     

准分子激光治疗白癜风的临床疗效与安全性研究

Objective To assess the efficacy and safety of 308 nm excimer laser in the treatment of different types of vitiligo at different stages. Methods A total of 128 patients with vitiligo, who had 317 depigmented patches, were recruited in this study and treated with 308 nm excimer laser once a week for at least 8 weeks. The degree of repigmentation was evaluated and adverse effects were recorded at the end of every treatment and last treatment. Results All patients received efficacy and safety evaluation. Of the 317 patches, 97.5% achieved repigmentation at different degrees, 71.8% got more than 25% repigmentation, and 50.8% got more than 75% repigmentation. The degree of repigmentation increased with the number of treatments. A better response was observed in the lesions on the face and neck than those on the mink and limbs, and in short-duration (<1 year) lesions than in long-duration (≥1 year) lesions. And the lesions on extremities and mueosa showed a poorer response compared with those at other sites. There was no statistical difference in clinical efficacy between active vitiligo and stable vitiligo, or between adults and children. Moreover, the treatment was well tolerated. Conclusion 308 nm excimer laser is effective in the treatment of vitiligo with rapid onset, favorable tolerability and few adverse effects.     

High expression of Ki-67 and cyclin D1 in invasive extramammary Paget's disease

BACKGROUND: Invasive extramammary Paget's disease (EMPD) is commonly associated with a poor prognosis. Although early detection of micro invasion can improve the prognosis, diagnosis is not always straightforward in some EMPD cases. Several clinical studies have proposed mechanisms underlying the increased invasiveness of EMPD; however, molecular markers indicative of the invasiveness have yet to be well characterized. OBJECTIVE: The purpose of this study was to identify a reliable immunohistochemical marker for predicting the risk of invasion and metastasis in EMPD cases. METHODS: A total of 32 specimens from 23 primary EMPD cases were analyzed by immunohistochemical staining. In formalin-fixed, paraffin-embedded tissue sections, immunolabeling of tumor cells were scored by stain intensity on a four-tiered scale. Using antibodies against several tumor proliferation markers, such as Her2, p53, Ki-67, cyclin D1 and Bcl-2, we determined the correlation between the expression of these molecular markers and the types of EMPD lesions (in situ, invasive or metastatic). RESULTS: In contrast to Her2, p53 and Bcl-2, which are similarly expressed among different types of lesions, Ki-67 and cyclin D1 are expressed at significantly higher levels in invasive lesions than in situ lesions (P<0.01 and P<0.05, respectively). Furthermore, the mean of the sum of Ki-67 and cyclin D1 expression scores was significantly higher in invasive lesions, compared to the scores obtained for in situ lesions. In addition, the difference was more significant (P相似文献   

Expression and prognostic significance of Stat5a and E-cadherin in extramammary Paget's disease

BACKGROUND: Stat5 has been shown to regulate the proliferation and inhibition of apoptosis in cancer cells. E-cadherin plays an important role in maintaining epithelial stability and is widely regarded as a prognostic marker in many types of human cancers. The expression of Stat5 has not been investigated in extramammary Paget's disease (EMPD). OBJECTIVES: To study the expression of Stat5a and E-cadherin protein in EMPD and to evaluate the relationships between them. METHODS: Thirty-six tissue samples from 34 cases with primary EMPD were subjected to immunohistochemical staining for Stat5a and E-cadherin. RESULTS: Twenty-nine of 30 in situ EMPD specimens were positive for Stat5a expression, and the staining pattern for Stat5a was mainly nuclear in the majority of Paget's cells. All four invasive specimens and two metastatic lymph node specimens were negative for Stat5a. Twenty-six of 30 in situ EMPD specimens expressed E-cadherin in more than 50% of tumor cells, and three of 30 in situ EMPD specimens expressed E-cadherin in less than 50% of tumor cells. One in situ EMPD specimen and one invasive specimen expressed E-cadherin in less than 25% of tumor cells. Three invasive specimens and two metastatic lymph node specimens were negative, with occasional membranous staining for E-cadherin. There is a significant correlation between the expression of Stat5a and E-cadherin. CONCLUSIONS: Our results showed that these proteins were found in in situ lesions, and it is speculated that these proteins may play some role in the prognosis/invasion of EMPD.     

Extramammary Paget's disease of the groin with underlying carcinoma and fatal outcome

Extramammary Paget's disease (EMPD) is considered to be an intraepithelial adenocarcinoma. Typically involved anatomical sites are the vulvar, perianal, perineal, scrotal and penile regions. Clinically, the lesions present as well-defined, moist, erythematous plaques usually accompanied by pruritus. An unusual feature of EMPD is its association with cutaneous, adnexal-structure adenocarcinomas and its association with internal malignancies. Histopathological examination shows epidermal acanthosis and elongated rete ridges. Paget's cells are large intraepidermal cells with a large nucleous and abundant pale cytoplasm. Recent studies of perianal and vulvar EMPD have described distinct immunohistochemical subtypes termed cutaneous and endodermal. Cutaneous EMPD is characteristically positive for cytokeratin (CK)7, negative for CK20, and positive for gross cystic disease fluid protein (GCDFP)15+, whereas endodermal EMPD shows a CK7+ CK20+ GCDFP15− phenotype. Surgery remains the treatment of choice, with either wide surgical excision or Mohs' micrographic surgery. We present a case of EMPD with an underlying carcinoma, which combined immunohistochemical findings suggestive of the cutaneous subtype (positive for CK7, GCDFP15, mucin (MUC)1, human epidermal growth factor receptor (HER)2/neu positive) and the endodermal subtype, frequently associated with internal malignancy (CK20, MUC2, CDX-2 positve); however, our patient had no associated internal malignancy.     

Gsk-3β、CD82和Axin1在乳房和乳房外Paget病中的表达

目的：检测Gsk-3β、CD82和Axin1在乳房和乳房外Paget病中的表达。方法：采用免疫组织化学方法检测20例乳房Paget病、20例乳房外Paget病及10例正常皮肤组织中Gsk-3β、CD82和Axin1的表达情况。结果：Gsk-3β在乳房Paget病、乳房外Paget病中的表达水平分别为(3.39±1.41)和(2.93±1.37),显著低于正常皮肤组织的(6.50±2.16),CD82表达水平分别为(6.05±2.14)和(3.90±1.75),显著低于正常皮肤组织的(10.68±1.11),Axin1表达水平分别为(2.39±1.49)和(2.77±1.64), 显著低于正常皮肤组织的(5.57±1.72)。Gsk-3β、CD82和Axin1在乳房和乳房外Paget病组织中的表达差异无统计学意义(P>0.05)。结论：Gsk-3β、CD82和Axin1在乳房和乳房外Paget病中低表达,可能与乳房和乳房外Paget病的发病有关。     

Cyclin D1、PCNA和C-erbB-2在乳房外Paget病中的表达及意义

目的研究c7clin D1、PCNA和C—erbB-2在乳房外Paget病中的表达及意义。方法用免疫组织化学技术检测28例乳房外Paget病的石蜡包埋组织及12例正常皮肤组织中Cyclin D1、PCNA和C—erbB-2的表达。结果CyclinDI在乳厉外Paget病组织中阳性率（92．86％）高于正常皮肤对照组（8．33％）,两者差异有统计学意义（P〈0．05）;PCNA在乳房外Paget病组织中阳性率（89．29％）显著高于正常皮肤对照组（16．67％）,两者差异有统计学意义（P〈0．01）;C—erbB-2在乳房外Paget病组织中阳性率（96．43％）高于正常皮肤对照组（8．33％）,两者差异有统计学意义（P〈0．05）。结论Cyclin D1、PCNA和C-erbB-2在乳房外Paget病组织中均呈高表达,其与乳房外Paget病的发生关系密切。     

Matrilysin-1 (MMP-7) and MMP-19 are expressed by Paget's cells in extramammary Paget's disease

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare malignant neoplasm of apocrine gland bearing skin characterized by intraepidermal proliferation of adenocarcinoma cells. Tumor growth depends on the ability of tumor cells to migrate by proteolysis and on angiogenesis. The matrix metalloproteinase (MMP) enzymes have been implicated in both of these processes in other types of skin cancer. METHODS: The expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-19 was analyzed by immuno- histochemistry and/or in situ hybridization in 27 EMPD and five mammary PD (MMPD) specimens. The distribution of laminin-5 (LN-5) and tenascin-C, two extracellular matrix proteins associated with tumor invasion, was studied by immunohistochemistry. RESULTS: MMP-7 (matrilysin-1) and MMP-19 were the most frequently expressed MMPs in Paget's cells. Overexpression of MMP-2, MMP-9, or MMP-13, which is seen in many cancers, was not evident in EMPD. LN-5 and tenascin-C positivity did not correlate with the level of invasion. MMP-7, MMP-13, and MMP-19 were detected abundantly in MMPD, while MMP-9 was absent. CONCLUSIONS: MMP expression did not generally associate with the level of invasion of EMPD. In three samples positive for MMP-7 and four samples positive for MMP-19, an underlying carcinoma was detected, suggesting the importance of these two MMPs as predictors of secondary EMPD or the putative origin of Paget's cells from the dermal adenocarcinoma cells of apocrine duct origin.     

乳房外Paget病中p-ATF2和p-STAT3的表达

目的探讨磷酸化活化转录因子2(p-ATF2)和磷酸化细胞信号传导与转录活化因子3(p-STAT3)在乳房外Paget病(EMPD)中的表达。方法采用免疫组化ABC法检测p-ATF2和p-STAT3在45例EMPD皮损石蜡包埋切片中的表达。结果在45例EMPD中,有43例高表达p-ATF2和p-STAT3。在8例进展性EMPD中,p-ATF2 (>95%)和p-STAT3(>92%)表达阳性细胞百分数均高于非进展性EMPD(P值均<0.01)。在EMPD中,p-ATF2阳性表达与p-STAT3阳性表达有高度相关性(r=0.97,P<0.001)。结论p-ATF2和p-STAT3在EMPD的发生和肿瘤进展机制中可能起一定的作用。     

Extramammary Paget''s disease:

We examined 32 cases (38 lesions) of extramammary Paget's disease (EMPD) in relation to comparative studies on intraductal carcinoma of the breast (ductal carcinoma in situ, DCIS) and apocrine adenocarcinoma (AAC). Lesions included scrotum (18 lesions), vulva (8), axilla (6), groin (3), penis (2) and chest wall (1), and the distribution was compatible with that of apocrine or supernumerary mammary glands. Histologically, extra-mammary Paget's and DCIS cells exhibited a large amount of a pale-stained cytoplasm. The cytoplasm of AAC cells frequently contained granules, was eosinophilic and differed from that of Paget's or DCIS cells. Immunohistochemical studies revealed positive reactions for polyclonal and monoclonal antibodies to carcinoembryonic antigen in all EMPD and most DCIS, but not in AAC. Recent studies have shown that extramammary Paget's cells exhibit characteristics of glandular epithelial cells and that most cases of EMPD are not accompanied by an underlying carcinoma. The results obtained in this study, coupled with data on the frequency of the supernumerary breasts, lead to the speculation that extramammary Paget's cells originate from ectopic mammary glands or from pluripotential germinative cells in the epidermis, capable of differentiating toward the mammary glands.     

乳房外Paget病中汗腺病理及免疫组化分析

目的：分析乳房外Paget病(EMPD)中汗腺上皮组织CK7和CEA的表达及临床意义。方法：应用免疫组化SP法对15例EMPD皮损和周边正常皮肤CK7和CEA的表达进行检测。结果：15例中有8例在汗腺腺体及导管部见CK7和CEA呈阳性，其中仅5例发现汗腺上皮细胞呈异常改变。结论：免疫组化方法在诊断和鉴别诊断EMPD中汗腺上皮细胞的不典型增生具有一定价值。